{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T18:35:48Z","timestamp":1778524548980,"version":"3.51.4"},"reference-count":95,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T00:00:00Z","timestamp":1570665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["#2013\/04088-0; #2014\/13324-1; 2008\/52130-7;2017\/02998-0"],"award-info":[{"award-number":["#2013\/04088-0; #2014\/13324-1; 2008\/52130-7;2017\/02998-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["#475357\/2013-2;#306298\/2013-9"],"award-info":[{"award-number":["#475357\/2013-2;#306298\/2013-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["G12MD007592;2G12MD007592"],"award-info":[{"award-number":["G12MD007592;2G12MD007592"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The microneme organelles of Toxoplasma gondii tachyzoites release protein complexes (MICs), including one composed of the transmembrane protein MIC6 plus MIC1 and MIC4. In this complex, carbohydrate recognition domains of MIC1 and MIC4 are exposed and interact with terminal sialic acid and galactose residues, respectively, of host cell glycans. Recently, we demonstrated that MIC1 and MIC4 binding to the N-glycans of Toll-like receptor (TLR) 2 and TLR4 on phagocytes triggers cell activation and pro-inflammatory cytokine production. Herein, we investigated the requirement for TLR2 heterodimerization and co-receptors in MIC-induced responses, as well as the signaling molecules involved. We used MICs to stimulate macrophages and HEK293T cells transfected with TLR2 and TLR1 or TLR6, both with or without the co-receptors CD14 and CD36. Then, the cell responses were analyzed, including nuclear factor-kappa B (NF-\u03baB) activation and cytokine production, which showed that (1) only TLR2, among the studied factors, is crucial for MIC-induced cell activation; (2) TLR2 heterodimerization augments, but is not critical for, activation; (3) CD14 and CD36 enhance the response to MIC stimulus; and (4) MICs activate cells through a transforming growth factor beta-activated kinase 1 (TAK1)-, mammalian p38 mitogen-activated protein kinase (p38)-, and NF-\u03baB-dependent pathway. Remarkably, among the studied factors, the interaction of MIC1 and MIC4 with TLR2 N-glycans is sufficient to induce cell activation, which promotes host protection against T. gondii infection.<\/jats:p>","DOI":"10.3390\/ijms20205001","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T03:07:11Z","timestamp":1570763231000},"page":"5001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Receptor Heterodimerization and Co-Receptor Engagement in TLR2 Activation Induced by MIC1 and MIC4 from Toxoplasma gondii"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5239-6965","authenticated-orcid":false,"given":"Fl\u00e1via","family":"Costa Mendon\u00e7a-Natividade","sequence":"first","affiliation":[{"name":"Laboratory of Immunochemistry and Glycobiology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (FMRP\/USP), Ribeir\u00e3o Preto SP 14049-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Duque Lopes","sequence":"additional","affiliation":[{"name":"Laboratory of Immunochemistry and Glycobiology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (FMRP\/USP), Ribeir\u00e3o Preto SP 14049-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-6530","authenticated-orcid":false,"given":"Rafael","family":"Ricci-Azevedo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunochemistry and Glycobiology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (FMRP\/USP), Ribeir\u00e3o Preto SP 14049-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Sardinha-Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Immunochemistry and Glycobiology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (FMRP\/USP), Ribeir\u00e3o Preto SP 14049-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Figueiredo Pinzan","sequence":"additional","affiliation":[{"name":"Laboratory of Immunochemistry and Glycobiology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (FMRP\/USP), Ribeir\u00e3o Preto SP 14049-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Paiva Alegre-Maller","sequence":"additional","affiliation":[{"name":"Laboratory of Immunochemistry and Glycobiology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (FMRP\/USP), Ribeir\u00e3o Preto SP 14049-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian","family":"L. Nohara","sequence":"additional","affiliation":[{"name":"Border Biomedical Research Center (BBRC), Department of Biological Sciences, University of Texas at El Paso (UTEP), El Paso, TX 79968, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"B. Carneiro","sequence":"additional","affiliation":[{"name":"Border Biomedical Research Center (BBRC), Department of Biological Sciences, University of Texas at El Paso (UTEP), El Paso, TX 79968, USA"},{"name":"Institute of Medical Biochemistry, Program of Molecular Biology and Biotechnology at Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro RJ 21941-599, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-0133","authenticated-orcid":false,"given":"Ademilson","family":"Panunto-Castelo","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeir\u00e3o Preto, University of S\u00e3o Paulo USP (FFCLRP\/USP), Ribeir\u00e3o Preto SP 14040-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"C. Almeida","sequence":"additional","affiliation":[{"name":"Border Biomedical Research Center (BBRC), Department of Biological Sciences, University of Texas at El Paso (UTEP), El Paso, TX 79968, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7425-0908","authenticated-orcid":false,"given":"Maria","family":"Roque-Barreira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunochemistry and Glycobiology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (FMRP\/USP), Ribeir\u00e3o Preto SP 14049-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/j.1574-6976.2011.00305.x","article-title":"Mechanisms of Toxoplasma gondii persistence and latency","volume":"36","author":"Sullivan","year":"2012","journal-title":"FEMS Microbiol. 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